Targeting Alzheimer's disease via phytochemicals from Artemisia campestris L.: GC/MS analysis with an integrated computational approach

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder requiring multi-target therapeutic strategies. In this study, phytochemicals from Artemisia campestris L., an ethnomedicinal plant native to Algeria, were evaluated as potential multitarget ligands against five AD-relevant proteins: acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), monoamine oxidase-B (MAO-B), β-secretase-1 (BACE-1), and glycogen synthase kinase 3β (GSK-3β), chosen for their roles in neurotransmission, amyloid processing, tau pathology, and oxidative stress. Molecular docking was performed using Glide XP, followed by ADMET prediction, 100-ns molecular dynamics simulations, MM-GBSA binding energy calculations, and DFT analysis. Among 25 compounds, dihydroartemisinic acid (C2) and ar-turmerone (C8) exhibited consistently stronger binding energies and higher dynamic stability across multiple targets compared with other constituents. These findings identify C2 and C8 as computationally predicted multitarget candidates that warrant experimental validation through in vitro enzyme inhibition and in vivo pharmacological studies.